Landscape of tumor-infiltrating T cell repertoire of human cancers.
Nat Genet
; 48(7): 725-32, 2016 07.
Article
em En
| MEDLINE
| ID: mdl-27240091
ABSTRACT
We developed a computational method to infer the complementarity-determining region 3 (CDR3) sequences of tumor-infiltrating T cells in 9,142 RNA-seq samples across 29 cancer types. We identified over 600,000 CDR3 sequences, including 15% that were full length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage, for infiltrating T cells in many tumors, except in brain and kidney cancers, resembled those for peripheral blood cells from healthy donors. We observed a strong association between T cell diversity and tumor mutation load, and we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers. Finally, we identified three potential immunogenic somatic mutations on the basis of their co-occurrence with CDR3 sequences. One of them, a PRAMEF4 mutation encoding p.Phe300Val, was predicted to result in peptide binding strongly to both MHC class I and class II molecules, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigens and tumor-reactive T cell clonotypes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
/
Linfócitos do Interstício Tumoral
/
Regiões Determinantes de Complementaridade
/
Mutação
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Proteínas de Neoplasias
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos